The general goals of the next grant period will continue to be the development of expedient regio- and stereochemically controlled synthetic methods for several of the most significant mycotoxins: trichothecenes, aflatoxins, PR-toxin and its analogs, and austalides. The synthetic routes to be pursued towards these environmental mycotoxins, with the exception of aflatoxins, will further focus upon the exploration of novel types of inter- and intramolecular Diels-Alder reactions. In particular, emphasis will be placed on the use of specific control elements to affect the stereochemical outcome of the intramolecular cycloaddition reaction. With regard to the study on the aflatoxins, we have unraveled a novel, biomimetic rearrangement reaction which has significant bearing on the biosynthetic process of the bis-furanoid or branched chain formation in the aflatoxins. This unique biomimetic reaction will be employed in the synthesis of aflatoxin B1 and its analogs. We would like to continue our studies in the area of mycotoxins with the following specific aims: 1) to complete the synthesis of verrucarol and anguidine through the use of the intramolecular Diels-Alder approach we have developed, 2) to develop new, regio- and stereochemically controlled synthetic methods amenable to the synthesis of the optically active 7,8-di- and 8-monooxygenated trichothecenes such as vomitoxin and T-2 toxin, 3) to develop novel enantiospecific synthetic routes to PR-toxin and austalide B and their respective analogs, and 4) to synthesize aflatoxin B1 and its analogs, in optically active forms, using a new rearrangement chemistry we have unraveled. Substances arising out of the proposed research, including many of the intermediates will be tested for their toxic-pharmacological activities as well as carcinogenic/antitumor activity by appropriate research groups.